The chance that chemotherapy will work in patients with bladder cancer is one in four. It is currently impossible to predict which patients will benefit from treatment and who will not. Urologist Dr. Tahlita Zuiverloon wants this to change. In a new research project, she is investigating the cause of chemotherapy resistance.
The project is funded by the prestigious R01 grant, which Prof. Dan Theodorescu of Cedars-Sinai in Los Angeles and Dr. James Costello of the University of Colorado in Denver received together with Zuiverloon. The total amount involved is $3 million.
The Rotterdam part of the research project focuses on bladder cancer organoids: three-dimensional mini bladder tumors, made of tumor cells from the patient. The organoids are cultured in the laboratory. This offers the opportunity to test outside the body how the tumor responds to chemotherapy.
‘Previous research has shown that the response of the organoid matches the clinical response in the patient. If the organoid continues to grow despite high concentrations of chemotherapy, we often see that chemotherapy does not work in the patient either. If we know this in advance, we can prevent exposure to toxic chemotherapy for specific patients.’
The organoids also provide opportunities to test new drugs and unravel the mechanism of chemotherapy resistance. To this end, Zuiverloon is collaborating with molecular biologist Dr. Tokameh Mahmoudi of Erasmus MC, who specializes in organoids. Zuiverloon and Mahmoudi have now established a biobank of bladder cancer organoids from 200 patients.
The R01 is the largest grant awarded by the US National Institute of Health (NIH). Competition for the funding is fierce, as evidenced by the 10 percent honorability rate. That they did manage to secure the funding, according to Zuiverloon, is due to the coming together of different disciplines within the collaboration with the American partners. This close relationship is the result of the Erasmus MC Fellowship during which Zuiverloon worked as a research fellow in Prof. Theodorescu’s lab from 2017 – 2019.
Zuiverloon is looking forward to spending a few days of her week on research again. ‘As an institute, if you want to perform at a high level in terms of research, you need time and space. I think it’s good that Erasmus MC is investing in that.’